Scope of Pharmacology

PHARMACOLOGY&TOXICOLOGY
AJIT KR YADAV
MSC BIOMEDICAL SCIENCE
DELHI UNIVERSITY

Definitions
• Pharmacology: is a science that studies the effect of the drugs on the
body..
• Medication: is a substance administered for diagnosis, cure, treatment,
mitigation or prevention.
• Prescription: the written direction for the preparation and the
administration of the drug.
The therapeutic effect: is the primary effect intended that is the reason
the drug is prescribed such as morphine sulfate is analgesia.
Side effect: secondary effect of the drug is one that unintended, side
effects are usually predictable and may be either harmless or little
undesirable effect.

Drug abuse: is an inappropriate intake of substance either continually or
periodically.
Drug dependence: is a persons reliance on or need to take drug or
substance there are two type of dependence:
Physiological dependence: is due to biochemical changes in the body
tissue these tissue come to require substance for normal function.
Psychological dependence: is emotional reliance on a drug to
maintain a since of wellbeing accompanied feeling of need
Drug habituation: denotes a mild form of psychological dependence.
Illicit drug: also called street drug are those sold illegally.

HISTORY OF PHARMACOLOGY
1. Francois Magendie (1783-1855), a French physiologist laid down
the dictum "Facts and facts alone are the basis of science."
Experimental procedures with animals are the testing grounds for
determination of drug action.
2. Claude Bernard (1813-1878) worked in Magendie's lab,
investigated the plant extract curare and proposed a site of action
for this agent.
3. Rudolph Buchheim (1820-1879). In 1847 Buchheim established the
first laboratory devoted to experimental pharmacology in the
basement of his home in Dorpat which is known as the cradle of
experimental pharmacology.
4. Oswald Schmiedeberg (1838-1921). In 1872 Schmiedeberg set up
an institute of pharmacology in Strasbourg, France (Germany at
that time)
5. J.N. Langley (1852-1925 and Sir Henry Dale (1875-1968) pioneered
pharmacology in England, taking a physiological approach.

6. The second world war was the impetus for accelerated research in
pharmacology (the war time antimalarial program) in the U.S., and
introduced strong analytical and synthetic chemical approaches.
Chemistry - Chemical structures of drugs can provide information
about mechanism of action, pharmacokinetics, stability, and metabolic
fate.
1. Structure-Activity Relationship - A modification of the chemical
structure of a drug may accentuate or diminish its pharmacological
effects, often providing clues as to the mechanism of action
2. Sites of Action - The organ or cellular target of drug action.
3. Drug Receptors - Macromolecules in cells or cell membranes with
which drugs interact to exert their effects.

Pharmacodynamics - The effect of the drug on the body. Pharmaco-dynamics is
the study of the relationship of drug concentration and the biologic effect
(physiological or biochemical).
For most drugs it is necessary to know the site of action and mechanism of action
at the level of the organ, functional system, or tissue. For example, the drug effect
may be localized to the brain, the neuromuscular junction, the heart, the kidney,
etc.
Often the mechanism of action can be described in biochemical or molecular
terms.
Most drugs exert effects on several organs or tissues, and have unwanted as well
as therapeutic effects. There is a dose-response relationship for wanted and
unwanted (toxic) effects.
Patient factors affect drug responses - age, weight, sex, diet, race, genetic factors,
disease states, trauma, concurrent drugs, etc.
Pharmacokinetics - The effect of the body on the drug.
To produce its characteristic effects, a drug must be present in appropriate
concentrations at its sites of action.

Pharmacokinetics: the interrelationship of the absorption, distribution, binding,
biotransformation, and excretion of a drug and its concentration at its locus of action.
1. Absorption (oral or parenteral) - A drug must be absorbed and achieve adequate
concentration at its site of action in order to produce its biological effects. Thus, when a
drug is applied to a body surface (e.g., g.i. tract, skin, etc.), its rate of absorption will
determine the time for its maximal concentration in plasma and at the receptor to
produce its peak effect.
2. Distribution - The blood, total body water, extracellular, lymphatic and cerebrospinal fluids
are involved in drug movement throughout the body. Depending upon its chemical and
physical properties, the drug may be bound to plasma proteins or dissolved in body fat,
delaying its progress to its sites of action or excretory mechanism.
3. Metabolism - This is how certain drugs are handled by the body in preparation for their
elimination and includes the fate of drugs-biotransformation (e.g., hydrolysis,
conjugation, oxidation-reduction).
4. Excretion - The kidney is the most important organ for drug excretion but the liver, lung
and skin are also involved in drug elimination. Drugs excreted in feces are mostly
derived from unabsorbed, orally ingested drugs or from metabolites excreted in the bile
and not reabsorbed by the intestine. The physical and chemical properties, especially
the degree of ionization of the drug, are important in the rate of excretion.
5. Biological Factors Modifying Pharmacokinetic Aspects - Normal variations occur in
population pharmacokinetic constants (absorption rates, elimination rates). Other
factors include age, weight, obesity, edema, concurrent diseases, other drugs (various
interactions including effects on protein binding or metabolic rate), diet, dose interval
and route of administration, genetic variations in elimination rate.

Clinical Pharmacology and Therapeutics
1. Indications and Therapeutic Uses - Emphasis is placed on the therapeutic use of drugs for
the treatment of disease in clinical pharmacology, internal medicine and therapeutics.
There are specific clinic disorders or disease entities for which a given drug may be
prescribed and the physician must weigh the potential benefit of drug use against the risks
of adverse effects.
2. Contraindications and Factors It is important to know that the presence of disease or organ
pathology may influence the actions of a drug. Conditions such as age, pregnancy,
concomitant administration of other drugs and disease may alter the patient's response to
a given drug.
3. Posology - Is a term describing dosage regimens. Consideration of dosage schedules is a part
of pharmacokinetics.
4. Bioavailability - The fraction of drug administered which is actually absorbed and reaches
the systemic circulation following drug administration. Preparations of the same drug by
different manufacturers may have a different bioavailability.
5. Prescription writing - It is important that the physician write clear, error-free directions for
the drug provider (pharmacist) and for the patient. Physicians must guard against
prescribing too many drugs, or preparations of little value. Drugs of unproven clinical value
should be avoided, as well as potentially toxic agents if drugs equally effective but less
dangerous are available. Risk-benefit and cost-benefit should be considered. Drugs may be
prescribed by generic name, since often a less expensive drug product can be obtained in
this way. A particular manufacturer may be specified if the physician has reason to believe
a better or more reliable preparation is available from that manufacturer.

Pharmacovigilance - The area of pharmacology that focuses on the effects of drugs on
patient safety. It involves the characterization, detection, and understanding of adverse
events associated with drug administration, including adverse drug reactions, toxicities,
and side effects that arise as a consequence of the short- or long-term use of drugs.
Adverse drug reactions, including drug-drug interactions, are estimated to be a major
cause of mortality of inpatients and also lead to significant increases in duration of
hospitalization. No drug is free of toxic effects. Examples of chemicals or drug-induced
toxicities are given below:
1. Allergic reactions - The number of serious allergic reactions to drugs involving
antigen-antibody reactions is low but when they occur the physician must have
sufficient knowledge to manage these problems.
2. Blood dyscrasias - These are very serious and sometimes fatal complications of drug
therapy. They include: agranulocytosis, aplastic anemia, hemolytic anemia,
thrombocytopenia and defects in clotting factors.
3. Hepatotoxicity and nephrotoxicity - Because many chemicals and drugs are
eliminated and metabolized by the liver and kidney, damage to these organs is seen
commonly.
4. Teratogenic effects - The thalidomide tragedy dramatically emphasized that drugs
may adversely influence fetal development.

5. Behavioral toxicity - This is a term used to describe suppression of normal
anxiety, reduction in motivation, impairment of memory and learning, distortion
of judgement, impairment of reflexes, adverse effects on mood, etc.
6. Drug dependence and drug abuse - The repeated administration of some
chemicals may lead to drug dependence. Drugs likely to be abused and upon
which drug dependence may develop are the various psychopharmacological
agents such as opiates, barbiturates, amphetamines, nicotine and ethanol.
Dependence on tobacco (nicotine) is also well known.
7. Carcinogenesis - Carcinogenesis is a delayed type of toxicity with a latency of
many years.
8. Pharmacogenetic toxicities - Certain genetically-predisposed individuals have a
markedly toxic reaction to certain otherwise safe drugs. Examples are prolonged
apnea after succinylcholine, or malignant hyperthermia associated with
anesthetics.

Chemical name: which includes information on the drugs molecular structure (e.g. 2-
acetoxybenzoic acid).
Trivial name: a common name, sometimes arising from historical uses, pre-dating the
use of formal naming conventions (e.g. acetylsalicylic acid, or ASA).
Generic name: a non-proprietary drug name (e.g. aspirin), adopted by an officially
recognized organization within each country.
Trade Name(s): the name for a drug whose formula, and/or mode of manufacture is
owned by a corporation under a patent or registered trademark (e.g. Bufferin ®). Drugs
can frequently be formulated in multiple ways (e.g. buffered vs non-buffered aspirin),
resulting in multiple trade names for the same active ingredient, as illustrated in Table 1.
TABLE 1: Proprietary (Trade) Names for Common Drugs
Acetaminophen CROCIN
Aspirin ® Acephen ® Marcaine ®
Bufferin ®Nortemp ®
Ecotrin ® Ofirmev ®
Empirin ®Panadol ®
Sloprin ® Tylenol ®
Due to the fact that drugs can have many trade names, pharmacologists most commonly
refer to drugs by their non-proprietary generic name, and not by their trade name(s).

Dose and Dosage Definitions
According to the American Medical Association (AMA) Manual of Style, the definitive
guide on medical writing and style, dose and dosage each have very specific meanings.
A dose refers to a specified amount of medication taken at one time. By contrast, the
dosage is the prescribed administration of a specific amount, number, and frequency of
doses over a specific period of time.
In other words, a dose is simply an amount ( weight) of a medication that is administered
at one specific time. Whereas, the dosage is the dose, or amount of drug, attached to a
time-frequency. A dosage guides a drug regimen.
Units for Doses
According to the AMA, drug doses are expressed in conventional metric mass units (for
example, milligrams or milligrams per kilogram) rather than in molar SI units. Moreover,
certain drugs (such as insulin or heparin) may be prepared as mixtures and have no
specific molecular weight, thereby precluding their expression in mass units.
Although other drug dose units such as drops (for ophthalmologic preparations), grains
(for aspirin), and various apothecary system measurements (eg, teaspoonfuls, ounces,
and drams) may be encountered clinically, these units generally are not used.

INTRODUCTION, PRINCIPLES AND HISTORY OF TOXICOLOGY

Introduction to Toxicology
• Toxicology is the study of the adverse effects of chemical or physical agents on living
organisms.
• A toxicologist is trained to examine and communicate the nature of those effects on human,
animal, and environmental health.
• Toxicological research examines the cellular, biochemical, and molecular mechanisms of
action as well as functional effects such as neurobehavioral and immunological, and assesses
the probability of their occurrence.
• Fundamental to this process is characterizing the relation of exposure (or dose) to the
response.
• Risk assessment is the quantitative estimate of the potential effects on human health and
environmental significance of various types of chemical exposures (eg, pesticide residues in
food, contaminants in drinking water).

•Hazard is the potential for the toxicity to be realized in a specific setting or situation.
•Risk is the probability of a specific adverse effect to occur. It is often expressed as the
percentage of cases in a given population and during a specific time period. A risk estimate
can be based upon actual cases or a projection of future cases, based upon extrapolations.
•Toxicity rating and toxicity classification can be used for regulatory purposes.
•Toxicity rating is an arbitrary grading of doses or exposure levels causing toxic effects. The
grading can be “supertoxic,” “highly toxic,” “moderately toxic” and so on.
• The most common ratings concern acute toxicity.
• Toxicity classification concerns the grouping of chemicals into general categories according
to their most important toxic effect. Such categories can include allergenic, neurotoxic,
carcinogenic and so on. This classification can be of administrative value as a warning and
as information.

What Do Toxicologists Do?
Most Toxicologists work to assess and understand how
chemicals affect living systems
• Develop mechanistic understanding of
effects
• Ensure safer chemical products
• Develop safer drugs & medicines
• Determine risks from chemical exposures
• Develop treatments for chemical
exposures
• Ensure a safe food and water supply
• Forensics

What are major areas of specialization in toxicology?
• Mechanistic toxicology (basic biology and chemistry)
• Descriptive toxicology (testing)
• Regulatory toxicology (rule making
and compliance)
• Risk assessment (modeling)
• Translational and clinical (applying basic research to patient care)

Mechanistic Toxicology
Focuses on how
• Chemicals produce adverse effects
• Biological systems protect themselves against adverse effects
Involves
• Cellular and Molecular Biology
• Chemistry, often xenobiotic metabolism
Xenobiotic: a chemical that is foreign to the organism

• How persistent is a chemical in the body?
• Are metabolic products toxic?
• Do test animals exhibit the same results as humans or
other species of concern?
Mechanistic Toxicology
Chemical research in toxicology usually investigates
metabolic transformations of drugs or potentially
hazardous chemicals

Descriptive Toxicology Toxicity Testing
• Assesses the concentration-dependent hazard a chemical may
present
• Human health
• Natural populations
• Results typically applied to
• Approval of product use
• Regulating allowable concentrations in the environment.

Descriptive Toxicology
Types of toxicity testing
• In vitro (test tube)—useful in detecting potential biochemical and
genetic effects
• Use model systems (bacteria, cultured animal cells, DNA
interactions)
• In vivo (animal)—are essential for detecting health effects
• Acute, chronic, multi-generation
• Experimental animals may be treated with high doses over a
lifetime to evaluate potential to cause cancer
• In silico (computer-based)—biological experiments conducted by
computer models; these depend on data previously collected in
other experiments

• Molecular and cellular studies in
toxicology often supplement toxicity
testing results to help ascertain chemical
hazard. They often unravel complex
processes that underlie an adverse
response.
• Use of toxicants can help determine the
function of proteins in complex
networks.
Descriptive Toxicology Toxicity Testing

Descriptive Toxicology
• Chemical Manufacturers
• Pharmaceutical Industry
• US Federal Agencies and Programs
• National Toxicology Program (NTP)
• Environmental Protection Agency (EPA)
• National Institute of Environmental Health
Sciences (NIEHS)
• Food and Drug Administration (FDA)
• State and Local Governmental Bodies
What private and public sectors invest in toxicity testing
that aims to protect human health?

Regulatory Toxicology
• Setting rules and assuring compliance
• Product registration
• Allowable concentrations in food or environmental media
• Technical and legal issues may require negotiation and gathering of new
information
• Risk and safety are estimated by total weight of evidence
• Toxicity evidence is the basis, but often rules are modified by political, legal
considerations, as well a technical feasibility

Regulatory Toxicology Risk Assessment
• Hazard identification
• Dose-response assessment
• Exposure characterization
• Identify unique effects of chemical
mixtures
• Risk assessment
• Risk characterization
• Right to know and understand
• Uncertainty characterization
Is the mathematical modeling process that yields estimates for safe or
allowable chemical concentrations

Translational
• Scientists work in multidisciplinary teams involving basic researchers,
clinicians, patient care providers, regulators, and ethics boards.
• Basic scientists provide new tools for use in patients and for assessment of
their impact, and clinical researchers make novel observations about the
nature and progression of disease that can lead to further basic research.
Translational science is the application of biomedical research and drug
development to efficiently use a promising drug in the right patient
circumstances and assess its efficacy in the human using
appropriate indicators such as biomarkers.

Graphical representation of the interconnections between different areas of toxicology.
A mechanistic toxicologist is concerned with identifying and understanding the
cellular, biochemical, and molecular mechanisms by which chemicals exert toxic
effects on living organisms.
The results of mechanistic studies are very important in many areas of applied
toxicology.
In risk assessment, mechanistic data may be very useful in demonstrating that an
adverse outcome (eg, cancer, birth defects) observed in laboratory animals is directly
relevant to humans.

• Enteral
via gastrointestinal tract (GIT).
• Oral
• Sublingual
• Rectal
• Parenteral administration = injections.
• Inhalation
• Topical application

.1
ENTERAL
.i
ORAL
Oral route is the most common route of
administration. It is safe, convenient, cheap
and does not require the services of a skilled
personnel.
Disadvantages
Some drugs are unpalatable and cause
irritation of the intestinal tract resulting in
nausea, vomiting and diarrhea, in particular if
these are given before meal.

Some drugs are destroyed by intestinal enzymes
e.g. insulin is destroyed by intestinal enzymes.
In case of emergency, when quick action of a drug is
desired this route is not suitable.
This route is not suitable in the cases of
unconscious patients.
There is a necessity for cooperation on the part
of patient.

Absorption may be slow, unpredictable and irregular
because of the presence of variable amounts of food
at various stages of digestion and acidity and alkalinity
of the digestive juices might have a great impact on
absorption of drugs.
Importantly, the blood from intestinal tract passes via
portal vein to the liver where the drug may be
metabolized to a great extent before being distributed
to the site of action.
Thus oral route is not recommended for drug
undergoing extensive FIRST PASS EFFECT.

Disadvantages
Advantages
Slow effect
No complete absorption
(Low bioavailability).
Destruction by GIT
First pass effect
GIT irritation
Food–Drug interactions
Drug-Drug interactions
Not suitable for vomiting,
unconscious, emergency.
Easy
Self use
Safe
Convenient
cheap
No need for
sterilization

Dosage forms
Capsules
Tablets
Syrup
Suspension
Tablets
Hard- gelatin
capsule Spansule
Soft- gelatin
capsule

SUBLINGUAL
The tablet is placed under the tongue and absorption form
oral mucosa is rapid and uniform. For example
nitroglycerine is effective when given sublingually but
ineffective when administered orally.
The reason is that the drug has very high lipid solubility.
In this route venous drainage from mouth (bucal cavity) is
poured into the superior vena cava and the drug is saved
from first-pass effect.
If nitroglycerine is given by oral route, the hepatic first-pass
effect is sufficient to preclude the appearance of any
intact nitroglycerine in the systemic circulation.

Disadvantages
Advantages
Not for
irritant drugs
Frequent use
• Rapid effect (Emergency)
• No first pass metabolism.
• High bioavailability
• No GIT destruction
• No food drug
interaction
Dosage form: friable tablet

RECTAL ADMINISTRATION
The drug may be given rectally for systemic effect
when the patient is either unconscious or
vomiting.
However, absorption from rectum is irregular
and incomplete and may cause irritation
of rectal mucosa.
Also 50% of the drug absorbed from rectum
passes through liver before entering the systemic
circulation thus first-pass effect cannot be fully
avoided.

The drugs administered rectally are in the form of
suppositories e.g. Ergotamine for the treatment
of migraine.
Another form of preparation for rectal
administration is the ENEMA i.e. a solution or
suspension of the drug in water or some other
vehicle.
Suppositories may also be given for local
treatment of rectal conditions e.g. benzocain is
used to relieve pain and itching caused by
haemorrhoids

Disadvantages
Advantages
Not for
– Irregular
absorption &
bioavailability.
– Irritation of
rectal mucosa.
Suitable for
–Vomiting & children.
&unconsciousness
– Irritant & Bad taste drugs.
– less first pass metabolism
(50%)
Dosage form:
suppository or enema

PAR-ENTERAL
(Par-beyond enteral-intestine)
The term parenteral administration implies the routes through
which the drug directly reaches the body fluids, by passing
the preliminary process of transport through the intestinal
wall or pulmonary alveoli which is an essential process when
drugs are taken orally, inhaled or administered rectally.
Advantages over oral route.
i) Drug is neither invaded nor destroyed by digestive
enzymes.
ii) A higher concentration of drug in blood may be achieved
because the hepatic metabolism of drug due to First-Pass
effect is avoided.

iii) Absorption is complete and predictable.
In emergency this method is particularly useful. If the
patient is unconscious, uncooperative or vomiting, the
Parenteral therapy becomes necessary.
Disadvantages of the parenteral route:
i) It is expensive because all the parenteral preparations
should be sterilized
ii) Asepsis must be maintained to avoid infection.
iii) An intravascular injection may accidentally occur when it is
not actually intended. Dentists administer thousands of local
anesthetic injections every day. Injection to a highly vascular area such as
pterygomandibular space during an inferior alveolar nerve block has a high risk
of intravascular needle entrance. Accidental intravascular injection of local
anesthetic agent with vasoconstrictor may result in cardiovascular and central
nervous system toxicity, as well as tachycardia and hypertension.
There are reports that indicate aspiration is not performed in every injection.
Pain may accompany or follow the injection.
It requires the services of a professionally skilled personnel.

Intradermal (I.D.) (into skin)
Subcutaneous (S.C.)
Intramuscular (I.M.)
Intravenous (I.V.) (into veins)
Intra-arterial (I.A.) (into arteries)
Intrathecal (I.T.) (cerebrospinal fluids )
Intraperitoneal (I.P.) (peritoneal cavity)
Intra-articular (Synovial fluids)
Following are the Parenteral routes:

Intradermal:-
Drug are injected into papillary layer of skin.
For example tuberculin injection for
montoux test and BCG vaccination for
active immunization against tuberculosis.
BCG: Bacille Calmette-Guerin

a) Subcutaneous:-
The drug is dissolved in a small volume of
vehicle and injected beneath the skin from
where the absorption is slow and uniform.
Substances causing irritation to the tissues
should not be injected otherwise they will
cause pain and necrosis (deadening of
tissues) at the site of injection.

A diabetic patient
making subcutaneous
injection
subcutaneous injection
in the mouse

when continuous presence of the drug in tissues is
needed over a long period. Moreover, the use of depot
preparations from which the drug is released more
slowly than it is from simple solution e.g. long-acting
insulins. Another form of the depot preparation is
subcutaneous implant.
In this case, a sterile pellet is implanted into
subcutaneous tissue instead of injecting drug solution
e.g. hormones are administered in this way. If a
vasoconstrictor agent is incorporated in a drug
solution, it retards the absorption e.g. adrenaline is
combined with local anesthetics to prolong the local
anesthesia.

b) Intramuscular:-
Injection is made deep into the muscle tissue.
In humans, the best site is deltoid muscle in
the shoulder or the gluteus muscle in the
buttocks.
This method is suitable for the irritating
substances that cannot be given by
subcutaneous route.
The speed of absorption from site of injection
is dependent on the vehicle used, absorption
is quick from aqueous solutions and slow from
oily preparations. Absorption is complete,
predictable and faster than subcutaneous
route.

Intramuscular injection in deltoid and gluteal
muscles

Intravenous:-
Drug solution in injected directly into the lumen of a
vein so that it is diluted in the venous blood.
The drug is carried to the Heart and circulated to
the tissues.
Drugs in oily vehicle or those that cause
haemolysis should not be given by this route.
Since the drug is introduced directly into blood, the
desired concentration of the drug is achieved
immediately which is not possible by any other
procedure.

This route is of prime importance in emergency. Also
certain irritant drugs could be given by this route.
Also this is the only route for giving large volume of
drugs e.g. blood transfusion.
However, there are certain disadvantages of this
procedure.
1. Once the drug is injected nothing can be done to
prevent its action.
2. I/v injection requires technical skill to minimize the
risk of leakage of irritant solution into the
surrounding tissues.
3. Air embolism may cause serious problems.

Intraperitoneal:-
The peritoneum offers a large absorbing surface
area from which drugs enter circulation rapidly
but primarily by way of portal vein. Hence First-
Pass effect not avoided.
This is probably the most widely used route of
drug administration in laboratory animals. In
human, it is very rarely employed due to the
dangers of infection and injury to viscera and
blood vessels.

Intra Medullary:-
The needle is introduced into marrow cavity and
effects are similar to those following intravenous
injection. This route is used when veins are not
available specially in children. In adults the
injection is made into marrow cavity of sternum
and under 3 years of age into that of tibia or
femur.
g) Intrathecal:-
Blood brain barrier often prevents the entry of
certain drugs into the central nervous system.

Also the blood CSF barrier prevents the approach of
drugs to the meninges.
Thus when local and rapid effects of drugs on
meninges are desired the drugs are injected into
Subarachnoid (between arachnoid mater and pia
mater) space and effects of the drugs are then
localized to the spinal nerves and meninges e.g.
intrathecal injection of streptomycin in tuberculosis
and meningitis is used by this route but with the
invention of third generation cephalosporins it is not
used any more to treat these conditions.
The injection of local anaesthetics for the induction of
spinal anaesthesia is given by this route.

(the three membranes covering the brain and
spinal cord from outside to inward are dura
mater, arachnoid mater and pia mater)
.

Intra articular:-
It is also known as intra synovial.
Sometimes drugs are injected into the
joint cavity to localize their action at the
site of administration e.g. Hydrocortisone
acetate in the treatment of rheumatoid
arthritis.
Local anesthetic is added to minimize pain
of injection.
Strict aspesis must be maintained to avoid
joint-infection

Intra-Cardiac:-
In cardiac arrest intracardiac injection of adrenaline
is made for resuscitation.
Intra-arterial:-
Sometimes a drug is injected directly into an artery
to localize its effects in a particular tissue or organ.
In human the use of this technique is restricted to the
injection of radio-opaque media for diagnostic
purposes.
A competent person is required to inject the drug intra
arterially. However, there is no fear of first-pass
effect when the drug is given by this route.

INHALATION
Inhalation or Pulmonary Absorption: Gaseous
and volatile drugs may be inhaled.
They are then absorbed by pulmonary endothelium
and mucous membrane of the respiratory tract and
reach circulation rapidly.
Volatile or gaseous anaesthetics such as halothane,
enflurane and nitrous oxide are administered by this
route.
Bronchodilators are generally given from inhalers in
aerosol form.
Now inhalers have been developed which allow the
supply of accurately metered doses of drugs and
extended the scope of this technique.

LOCAL OR TOPIOCAL APPLICATION: Skin
Drugs applied locally on the skin are poorly
absorbed through the epidermis. However,
dermis is permeable to many solutes. Thus
systemic absorption of drugs occurs more readily
through abraded, burned or denuded skin.
Inflammation and other conditions that enhance
cutaneous blood flow also promote absorption.
Drugs are applied in the form of ointments,
pastes, poultice and cream to the skin for their
local action. However, absorption through skin
can be increased by suspending the drug in an
oily vehicle and rubbing the preparation into the
skin. This administration is inunction.

Mucous Membranes:-
Drugs are applied onto the various mucous membranes
for their local action
Mouth and Pharynx:-
Bitters are used for their reflex action to improve
digestion. Boroglycerine and gentian violet paint (as
astringent) are used for their effects on buccal mucosa.
Stomach & Intestine:-
Antacids (to neutralize secreted HCl) and emetics ( to
induce emesis) are used for their local effect
iii) Rectum:-
Drugs are applied in the form of suppository
or enemas e.g. glycerin suppository for their
local action. Drugs are employed for relief of
itching and pain in haemorrhoid.

Respiratory Tract:-
In infections of respiratory tract, tincture
benzoin costeam inhalations give relief from
nasal congestion, phenylephrine nasal drops are
also used for nasal congestion.
Vagina:-
The drugs are used in the form of pessary or
tablet to treat the vaginal infections. Although
this method can be applied for the drugs that are
absorbed through vaginal mucous membrane
into the circulation, it is restricted to the local
treatment of vaginal conditions

Conjunctivae:-
Mydriatics ( to dilate pupil), miotics (to
constrict the pupil), local anaesthetics antiseptics
and antibiotics are applied to the conjunctivae for
their local action.
Conjunctiva: The delicate membrane lining
the eyelids and covering the eye ball

Disadvantages
Advantages
– Infection
– Sterilization.
– Pain
– Needs skill
– Anaphylaxis
– Expensive.
• high bioavailability
• Rapid action (emergency)
• No first pass metabolism
Suitable for
–Vomiting &unconsciousness
– Irritant & Bad taste drugs.
– No gastric irritation
– No food-drug interaction
Dosage form:
Vial or ampoule

Produce local effect to
Skin (percutaneous) e.g. allergy testing,
topical local anesthesia
Mucous membrane of respiratory tract
(Inhalation) e.g. asthma
Eye drops e.g. conjunctivitis
Ear drops e.g. otitis externa
Intranasal, e.g. decongestant nasal spray

Disadvantages
Advantages
Only few
drugs can be
used
• Mucous membrane of
respiratory system
• Rapid absorption
(large surface area)
•Provide local action
• Minor systemic effect
• Low bioavailability
• Less side effects.
• No first pass effect
Dosage form: aerosol, nebulizer

a medicated adhesive patch applied to skin
* Slow effect (prolonged drug action)
* produce systemic effect
e.g. the nicotine patches

• Is the fraction of unchanged drug that enters systemic circulation after
administration and becomes available to produce action
• I.V. provides 100% bioavailability.
• Oral usually has less than I.V.
• Bio = AUC oral / AUC IV X 100

Factors Affecting Bioavailability:
 Molecular weight of drug.
Drug Formulation (ease of dissolution).
(solution > suspension > capsule > tablet)
 Drug solubility of the drug
 Chemical instability in gastric pH
(Penicillin & insulin )
 First pass metabolism reduces bioavai

Factors Affecting Bioavailability (BAV):
 Blood flow to absorptive site
• Greater blood flow increases
bioavailability
• Intestine has greater blood flow than
stomach
 Surface area available for absorption.
• Intestinal microvilli increases it
Rate of gastric emptying
• rapid gastric emptying fast transit
to intestine
 pH of gut

Intestinal motility (Transit Time)
• Diarrhea reduce absorption
Drug interactions
Food
• slow gastric emptying
• generally slow absorption
• Tetracycline, aspirin, penicillin V

Scope of Pharmacology

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Scope of Pharmacology